Investigate the Efficacy of Using NMN to Improve Embryo Development Capacity.

Official title

Investigate the Efficacy of Using NMN to Improve Embryo Development Capacity and IVF Success Rate in Patients Who Have Experienced IVF Failures.

Overview

The objective of this study is to investigate the efficacy of NMN supplementation in enhancing embryo developmental capacity and improving IVF success rates in patients experiencing IVF failures.

Detailed description

Reproductive aging is an irreversible process characterized by a decline in oocyte quality, posing a significant challenge to fertility and often leading to unsuccessful outcomes in assisted reproductive technologies. Repeated ART failures can result in substantial burdens for patients, both financially and emotionally. Extensive clinical and preclinical data have established a strong correlation between age-related decline in egg quality and mitochondrial deterioration, resulting in decreased energy production within oocytes. Notably, a reduction in nicotinamide adenine dinucleotide (NAD+ / NADH) concentrations, a crucial redox cofactor and enzyme-substrate essential for energy metabolism, DNA repair, and epigenetic homeostasis, has been observed in various tissues with age.

Recent studies on mice have indicated that Nicotinamide mononucleotide supplementation may mitigate the age-related decline in NAD(P)H levels, enhancing the quality of aged oocytes. This improvement is achieved by promoting both nuclear and cytoplasmic maturation, ensuring euploidy and fertilization competence, ultimately leading to an increased ovulation rate and improved fertility. Moreover, NMN has been shown to restore mitochondrial function in aged oocytes, effectively suppressing the accumulation of reactive oxygen species and DNA damage, and subsequently reducing apoptosis.

Clinical studies have further corroborated the safety and tolerability of NMN supplementation, with daily oral doses of up to 900 mg demonstrating an increase in blood NAD concentrations. Furthermore, research suggests that a daily oral dose of 900 mg maximizes clinical efficacy, as evidenced by blood NAD concentration and physical performance.

This study adopts a triple-blind, randomized, placebo-controlled, prospective pilot study design. This prospective study aims to evaluate the effects of dietary supplementation with 900mg of NMN on ART outcomes in individuals experiencing in vitro fertilization failures attributed to compromised oocyte and embryo quality.

Interventions

• Dietary supplement NMN capsule
  Total of 900mg/day for 8 weeks
• Other Placebo
  NMN-free placebo capsules for 8 weeks

Primary outcome measures

• Embryo development rate [Time frame: Up to 8 weeks post-intervention]
• Changes in metabolic status [Time frame: Up to 8 weeks post-intervention]
• Clinical pregnancy rate [Time frame: Up to 12months post-intervention]
• Embryo development rate [Time frame: Up to 8 weeks post-intervention]
• Embryo development rate [Time frame: Up to 8 weeks post-intervention]

Secondary outcome measures (10)

• Live Birth rates [Time frame: Up to 24 months post-intervention]
• Endocrine hormones including AMH [Time frame: Up to 8 weeks post-intervention]
• Average egg retrieval capacity per person [Time frame: Up to 8 weeks post-intervention]
• Additional in vitro fertilization - outcome indicators [Time frame: Up to 8 weeks post-intervention]
• Chemical pregnancy rate [Time frame: Up to 12months post-intervention]
• Pregnancy complication [Time frame: Up to 24 months post-intervention]
• Abortion rate [Time frame: Up to 24 months post-intervention]
• Additional in vitro fertilization - outcome indicators [Time frame: Up to 8 weeks post-intervention]
• Additional in vitro fertilization - outcome indicators [Time frame: Up to 8 weeks post-intervention]
• Additional in vitro fertilization - outcome indicators [Time frame: Up to 8 weeks post-intervention]

Eligibility criteria

Inclusion criteria

• Agree to participate in the study
• 32-42 years old
• Having at least one previous embryo implantation failure
• History of low Embryo quality at day3 or day5 (according to Veeck's and Gardner's Criteria)
• No major uterine or ovarian abnormalities
• BMI level 18-25kg/m2

Exclusion criteria

• Ovarian endometriosis with Chocolate cysts (AFS type 3 and 4)
• Patients who have taken different supplements such as coenzyme Q10, vitamin E, carnitine,niacin, nicotinamide, or other vitamin B3-related etc. within the previous month
• Any medical contraindication of oocyte retrieval or subsequent procedures
• Couples where the husband presents with severe sperm abnormalities
• Couples where the husband presents \<5 million/mL motile sperm
• Uterine structural anomalies
• Polycystic ovaries
• Premature ovarian failure
• Individuals who need regular medication to treat chronic diseases such as diabetes, hypertension, gout, hyperuricemia, etc.
• Individuals who need drug treatment for any mental illness such as epilepsy and depression.
• Individuals who suffer from infectious diseases such as hepatitis B, active tuberculosis, AIDS, etc.
• Cancer patients or receiving chemo/radiotherapy treatment within the past 3 years.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Basic science

Study locations

Japan · 1 center

• IVF Namba Clinic, Sankaky Medical Corporation — Osaka

Publications

• Huang H. A Multicentre, Randomised, Double Blind, Parallel Design, Placebo Controlled Study to Evaluate the Efficacy and Safety of Uthever (NMN Supplement), an Orally Administered Supplementation in Middle Aged and Older Adults. Front Aging. 2022 May 5;3:851698. doi: 10.3389/fragi.2022.851698. eCollection 2022. PMID 35821806
• Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. The efficacy and safety of beta-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Geroscience. 2023 Feb;45(1):29-43. doi: 10.1007/s11357-022-00705-1. Epub 2022 Dec 8. PMID 36482258
• Miao Y, Cui Z, Gao Q, Rui R, Xiong B. Nicotinamide Mononucleotide Supplementation Reverses the Declining Quality of Maternally Aged Oocytes. Cell Rep. 2020 Aug 4;32(5):107987. doi: 10.1016/j.celrep.2020.107987. PMID 32755581
• Bertoldo MJ, Listijono DR, Ho WJ, Riepsamen AH, Goss DM, Richani D, Jin XL, Mahbub S, Campbell JM, Habibalahi A, Loh WN, Youngson NA, Maniam J, Wong ASA, Selesniemi K, Bustamante S, Li C, Zhao Y, Marinova MB, Kim LJ, Lau L, Wu RM, Mikolaizak AS, Araki T, Le Couteur DG, Turner N, Morris MJ, Walters KA, Goldys E, O'Neill C, Gilchrist RB, Sinclair DA, Homer HA, Wu LE. NAD+ Repletion Rescues Female Fe PMID 32049001
• Schultz MB, Sinclair DA. Why NAD(+) Declines during Aging: It's Destroyed. Cell Metab. 2016 Jun 14;23(6):965-966. doi: 10.1016/j.cmet.2016.05.022. PMID 27304496
• Bentov Y, Yavorska T, Esfandiari N, Jurisicova A, Casper RF. The contribution of mitochondrial function to reproductive aging. J Assist Reprod Genet. 2011 Sep;28(9):773-83. doi: 10.1007/s10815-011-9588-7. Epub 2011 May 27. PMID 21617930
• Hashimoto S, Morimoto Y. Mitochondrial function of human embryo: Decline in their quality with maternal aging. Reprod Med Biol. 2022 Dec 21;21(1):e12491. doi: 10.1002/rmb2.12491. eCollection 2022 Jan-Dec. PMID 36570768

Identifiers

NCT: NCT06629636 · IVFJapan202402

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗